Muendlein A, Saely C H, Marte T, Schmid F, Koch L, Rein P, Langer P, Aczel S, Drexel H
Vorarlberg Institute for Vascular Investigation and Treatment, A 6800 Feldkirch, Austria.
Atherosclerosis. 2008 Jul;199(1):179-86. doi: 10.1016/j.atherosclerosis.2007.10.030. Epub 2008 Mar 4.
The single nucleotide polymorphisms (SNPs) apolipoprotein E (APOE) epsilon3/epsilon2/epsilon4, cholesteryl ester transfer protein (CETP) TaqIB, and apolipoprotein C3 (APOC3) -482 C>T have been associated with an atherogenic lipid profile and, in some studies, with increased cardiovascular risk. However, no data exist on their combined impact on atherosclerotic disease. We therefore aimed at investigating the combined impact of these SNPs on the presence of angiographically determined coronary artery disease (CAD). Genotyping was performed in 557 consecutive Caucasian patients undergoing coronary angiography for the evaluation of CAD. From the individual SNPs, only the APOE epsilon3epsilon4/epsilon4epsilon4 genotype was significantly associated with an increased risk of significant coronary stenoses with lumen narrowing >or=50% (odds ratio (OR)=1.77 [1.16-2.71]; p=0.008). However, the risk of CAD strongly increased when more than one of the analysed genetic variants was present: ORs were 2.74 [1.29-5.83]; p=0.009 for patients with both the APOE epsilon3epsilon4/epsilon4epsilon4 and the CETP B1B1 genotype, 1.97 [1.06-3.66]; p=0.031 for patients with both the APOE epsilon3epsilon4/epsilon4epsilon4 genotype and the APOC3 -482T allele, 2.12 [1.31-3.44]; p=0.002 for patients with both the CETP B1B1 genotype and the APOC3 -482T allele, and 3.99 [1.57-13.79]; p=0.029 for patients with all three variants. Multivariate analyses confirmed these results. We conclude that there are strong synergistic effects of the APOE epsilon3/epsilon2/epsilon4, the CETP TaqIB, and the APOC3 -482 C>T polymorphisms on their association with CAD.
单核苷酸多态性（SNP）载脂蛋白E（APOE）ε3/ε2/ε4、胆固醇酯转运蛋白（CETP）TaqIB以及载脂蛋白C3（APOC3）-482 C>T与致动脉粥样硬化血脂谱相关，并且在一些研究中与心血管风险增加相关。然而，尚无关于它们对动脉粥样硬化疾病联合影响的数据。因此，我们旨在研究这些SNP对血管造影确定的冠状动脉疾病（CAD）存在情况的联合影响。对557例连续接受冠状动脉造影以评估CAD的白种人患者进行基因分型。在各个SNP中，只有APOE ε3ε4/ε4ε4基因型与管腔狭窄≥50%的显著冠状动脉狭窄风险增加显著相关（比值比（OR）=1.77 [1.16 - 2.71]；p = 0.008）。然而，当存在一个以上分析的基因变异时，CAD风险显著增加：对于同时具有APOE ε3ε4/ε4ε4和CETP B1B1基因型的患者，OR为2.74 [1.29 - 5.83]；p = 0.009；对于同时具有APOE ε3ε4/ε4ε4基因型和APOC3 -482T等位基因的患者，OR为1.97 [1.06 - 3.66]；p = 0.031；对于同时具有CETP B1B1基因型和APOC3 -482T等位基因的患者，OR为2.12 [1.31 - 3.44]；p = 0.002；对于具有所有三种变异的患者，OR为3.99 [1.57 - 13.79]；p = 0.029。多变量分析证实了这些结果。我们得出结论，APOE ε3/ε2/ε4、CETP TaqIB以及APOC3 -482 C>T多态性在与CAD的关联中存在强烈的协同效应。
